In silico analysis of microRNAS targeting the HLA-G 3' untranslated region alleles and haplotypes

Hum Immunol. 2009 Dec;70(12):1020-5. doi: 10.1016/j.humimm.2009.07.028. Epub 2009 Aug 5.

Abstract

It has been reported that microRNAs (miRNA) may have allele-specific targeting for the 3' untranslated region (3' UTR) of the HLA-G locus. In a previous study, we reported 11 3'UTR haplotypes encompassing the 14-bp insertion/deletion polymorphism and seven SNPs (+3003 T/C, +3010 C/G, +3027 C/A, +3035 C/T, +3142 C/G, +3187 A/G, and +3196 C/G), of which only the +3142 C/G SNP has been reported to influence the binding of miRNAs. Using bioinformatics analyses, we identified putative miRNA-binding sites considering the haplotypes encompassing these eight polymorphic sites, and we ranked the lowest free energies that could potentially lead to an mRNA degradation or translational repression. When a specific haplotype or a particular SNP was associated with a miRNA-binding site, we defined a free energy difference of 4 kcal/mol between alleles to classify them energetically distant. The best results were obtained for the miR-513a-5p, miR-518c*, miR-1262 and miR-92a-1*, miR-92a-2*, miR-661, miR-1224-5p, and miR-433 miRNAs, all influencing one or more of the +3003, +3010, +3027, and +3035 SNPs. The miR-2110, miR-93, miR-508-5p, miR-331-5p, miR-616, miR-513b, and miR-589* miRNAs targeted the 14-bp fragment region, and miR-148a, miR-19a*, miR-152, mir-148b, and miR-218-2 also influenced the +3142 C/G polymorphism. These results suggest that these miRNAs might play a relevant role on the HLA-G expression pattern.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Alleles
  • Base Sequence
  • Binding Sites
  • Computational Biology
  • Gene Expression Regulation*
  • HLA Antigens / genetics*
  • HLA-G Antigens
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide

Substances

  • 3' Untranslated Regions
  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • MicroRNAs